Hepatocellular proliferation and development of hepatocellular carcinoma: a case-control study in chronic hepatitis C

Patients with hepatitis C have an increased risk of developing hepatocellular carcinoma (HCC). This is related to the stage of chronic liver disease, as characterized histologically by hepatic fibrosis and architectural distortion, but it is unclear whether histological markers can define the risk of developing HCC. We conducted a case-control immunohistochemical study of Ki-67, a marker for hepatocellular proliferation, in livers of 18 patients who had developed HCC more than 2 years after the biopsy specimen had been taken. Using conditional logistic regression analysis, the results were compared with 18 selected controls, who were age-matched patients with hepatitis C of similar histological stage who had not developed HCC. We also examined livers for cellular dysplasia, p53 mutations, and bcl-2 overexpression, and assessed whether the results could be correlated with demographic and disease-related variables, such as gender, region of birth, alcohol consumption, severity of liver disease, HCV genotype, and markers of hepatitis B virus (HBV) infection. Livers from patients who developed HCC were more often positive for Ki-67 (13 of 18 [72%] v 9 of 18 [50%]; P = .06) and tended to have higher mean Ki-67 scores (6 +/- 7.5 v 3 +/- 4.4; P = .10) compared with control cases. In the HCC-predisposed group, three livers showed large cell dysplasia, two were positive for p53 mutations, and two for bcl-2 overexpression. In contrast, in the non-HCC group, only one case had dysplasia, and none were positive for immunostaining for p53 or bcl-2 mutations. With the exception of one case, all livers with large cell dysplasia or p53 mutations and bcl-2 overexpression were also positive for Ki-67. Twelve (55%) of the 22 Ki-67-positive cases were anti-HBc-positive in the serum, in contrast to 2 of 14 (14%) patients in the Ki-67-negative group (P = .01). Patients with evidence of past infection with HBV were more often Ki-67 positive than those who had no evidence of past infection (85% [11 of 13] v 45% [10 of 22]; P = .02). There were no other associations between demographic or disease-related variables and Ki-67 expression. Increased hepatocellular proliferative activity, as assessed by Ki-67 expression, may be one factor indicative of an increased risk of developing HCC among patients with chronic hepatitis C. Furthermore, past infection with HBV appears to be an important correlate of increased hepatocellular proliferation in hepatitis C.     

Salbutamol enhances isotonic contractile properties of rat diaphragm muscle

The effects of the beta2-adrenoceptor agonist salbutamol (Slb) on isometric and isotonic contractile properties of the rat diaphragm muscle (Diamus) were examined. A loading dose of 25 microg/kg Slb was administered intracardially before Diamus excision to ensure adequate diffusion. Studies were then performed with 0.05 microM Slb in the in vitro tissue chamber. cAMP levels were determined by radioimmunoassay. Compared with controls (Ctl), cAMP levels were elevated after Slb treatment. In Slb-treated rats, isometric twitch and maximum tetanic force were increased by approximately 40 and approximately 20%, respectively. Maximum shortening velocity increased by approximately 15% after Slb treatment, and maximum power output increased by approximately 25%. During repeated isotonic activation, the rate of fatigue was faster in the Slb-treated Diamus, but both Slb-treated and Ctl Diamus fatigued to the same maximum power output. Still, endurance time during repetitive isotonic contractions was approximately 10% shorter in the Slb-treated Diamus. These results are consistent with the hypothesis that beta-adrenoceptor stimulation by Slb enhances Diamus contractility and that these effects of Slb are likely mediated, at least in part, by elevated cAMP.     

Predictive value of dialysis adequacy and nutritional indices for mortality and morbidity in CAPD and HD patients. A longitudinal study

BACKGROUND: The effects of dialysis inadequacy on patient survival and nutritional status and that of malnutrition on survival have not been clearly assessed. Studies comparing dose/mortality and morbidity curves on continuous ambulatory peritoneal dialysis (CAPD) and on haemodialysis (HD) are also needed, to assess adequate treatment on CAPD. METHODS: We have evaluated the effects of age, 13 pretreatment risk factors, serum albumin, transferrin, normalized protein catabolic rate, Kt/V, normalized weekly creatinine clearance, residual renal function and subjective global assessment of nutritional status on survival and morbidity, in a 3-year prospective study of 68 CAPD and 34 HD patients. RESULTS: Survivals did not differ for CAPD and HD patients. In the Cox hazard regression model, age, peripheral vasculopathy, serum albumin < 3.5 g/dl and Kt/V < 1.0/treatment on HD and < 1.7/week on CAPD were independent factors negatively affecting survival. On the contrary, adjusted survivals were not affected by gender, modality, other comorbid factors, normalized protein catabolic rate, or subjective global assessment of nutritional status. Persistence of residual renal function significantly improved survival. Observed and adjusted survival did not significantly differ for CAPD and HD patients with either low (HD, < 1.0/treatment; CAPD, < 1.7/week) or high ( > or = 1.0 and > or = 1.7) Kt/V. On HD, adjusted survivals were similar for 1.0 < or = Kt/V < 1.2 or > or = 1.2. On CAPD, Kt/V > or = 1.96/week was associated with definitely better survival, with only one death/23 patients versus 19/45, with Kt/V < or = 1.96. Survival was not different for 1.96 < or = Kt/V < 2.03 and > or = 2.03. Normalized weekly creatinine clearance and wKt/V were positively related on CAPD (r 0.39, P < 0.01) and wKt/V = 1.96 corresponded to 58 litres of normalized weekly creatinine clearance. CONCLUSIONS: Indices of adequacy were predictors of mortality and morbidity, both on CAPD and HD, whereas normalized protein catabolic rate and subjective global assessment of nutritional status were not. Serum albumin did not decrease during dialysis; hence its predictive effect for survival is due to the predialysis condition and not to dialysis-induced malnutrition.     

Cytogenetic abnormalities in pediatric myelodysplastic syndrome: a report of three cases

Three consecutive cases of pediatric myelodysplastic syndrome (MDS) diagnosed over a three-year period in Queen Mary Hospital, Hong Kong, were described. Depending on the classification system used, they comprised two cases of chronic myelomonocytic leukemia (CMMoL) of which one can be reclassified as juvenile chronic myeloid leukemia (JCML) and one cases of refractory anemia with excess of blasts (RAEB) or an alternative diagnosis of atypical CML. Cytogenetic abnormalities were detected in all of them on examination of bone marrow cells. Of the two CMMoL, one had monosomy 21, whereas the other had hypodiploidy. The patient with RAEB had a complex karyotype of 46,X,del(X)(q24),t(1;7) (p22;q32),add(15)(q26)(8). The balanced translocation (1;7) seen in this patient was exceedingly rare and, to the best of our knowledge, was reported only twice in the literature. The karyotypic abnormalities that we saw in our patients were not well recognized in pediatric MDS. This report emphasizes the importance of cytogenetic study in children suspected of suffering from MDS, which remains a rare disorder of childhood, and a need to rationalize current classification schemes.     

The IPCS Collaborative Study on Neurobehavioral Screening. I. Background and genesis

Numerous events over several years culminated in recognition of the need to explicitly evaluate the nervous system as a potential target for environmental chemicals. Based on recommendations from several international expert panels, the International Programme on Chemical Safety (IPCS) sponsored the Collaborative Study on Neurobehavioral Screening Methods. A Steering Committee was created to oversee the project, develop the testing protocol, recruit participating laboratories and review and analyze the data. The protocol specified the tests, the chemicals (supplied from a common source) and the exposure conditions (acute and repeated dosing). Test methods were based upon existing practices in toxicological screening as well as recent advances in neurotoxicity screening. Chemicals were selected to produce different profiles of neurobehavioral effects. Considerable latitude was afforded the participating laboratories in the choice of several key variables (e.g., strain of rat, testing device for motor activity assessment) that could potentially affect the results of the experiments. The approach therefore provided a standardized yet flexible protocol for evaluating the reproducibility of neurobehavioral screening data in diverse laboratory settings.     

The stomach of the sambar deer (Cervus unicolor unicolor)

In New Zealand, the sambar deer is reported to feed on a variety of grasses and browse material. In the specimens studied, the average volume of the sambar rumen was about 151. Thick, non-papillated pillars divided the rumen into a saccus dorsalis and a saccus ventralis. The lining of the rumen was covered with papillae; those in the roof area were short and poorly developed. The omasum was a well-developed organ with 47-71 (mean 57) laminae. These were covered with short and poorly developed papillae. It is concluded that these sambar deer stomachs were typical of a grass-roughage feeder. This contrasts with the previous classification of the sambar deer as an intermediate feeder.     

Analytical solutions to a multicylinder somatic shunt cable model for passive neurones with spines

A multicylinder somatic shunt model for spiny, passive neurones is considered. The spines are modelled as a continuum (after Baer & Rinzel, 1991), coupled through the spread of dendritic voltage. A general solution is developed and a relationship governing the contribution of dendrites, soma, and spines to the voltage response is derived.